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Biomedical subjects

G A Wray

Publications and source records attributed to G A Wray.

At least 19 recordsLinked to original sources

Rapid evolution of cis-regulatory sequences via local point mutations.

Although the evolution of protein-coding sequences within genomes is well understood, the same cannot be said of the cis-regulatory regions that control transcription. Yet, changes in gene expression are likely to constitute an important component of phenotypic evolution. We simulated the evolution of new transcription factor binding sites via local point mutations. The results indicate that new binding sites appear and become fixed within populations on microevolutionary timescales under an assumption of neutral evolution. Even combinations of two new binding sites evolve very quickly. We predict that local point mutations continually generate considerable genetic variation that is capable of altering gene expression.

Animals↗

Evolution of regeneration and fission in annelids: insights from engrailed- and orthodenticle-class gene expression.

The recent explosion of information on the role of regulatory genes in embryogenesis provides an excellent opportunity to study how these genes participate in post-embryonic developmental processes. We present a detailed comparison of regulatory gene expression during regeneration and asexual reproduction (by fission) in the segmented worm Pristina leidyi (Annelida: Oligochaeta). We isolated three genes from Pristina, one homolog of engrailed and two homologs of orthodenticle, and characterized their expression in different developmental contexts. In situ hybridization studies on worms undergoing normal growth, regeneration and fission demonstrate that in all three processes, Pl-en is expressed primarily in the developing nervous system, and Pl-Otx1 and Pl-Otx2 are expressed primarily in the anterior body wall, foregut and developing nervous system. Our data reveal extensive similarities between expression during regeneration and fission, consistent with the idea that similar developmental processes underlie these two types of development. Thus, we argue that in these annelids fission may have evolved by recruitment of regenerative processes. Furthermore, by comparing our data to existing data from leech embryos, we find evidence that embryonic processes are re-deployed during regeneration and fission.

Amino Acid Sequence↗

A sea urchin genome project: sequence scan, virtual map, and additional resources.

Results of a first-stage Sea Urchin Genome Project are summarized here. The species chosen was Strongylocentrotus purpuratus, a research model of major importance in developmental and molecular biology. A virtual map of the genome was constructed by sequencing the ends of 76,020 bacterial artificial chromosome (BAC) recombinants (average length, 125 kb). The BAC-end sequence tag connectors (STCs) occur an average of 10 kb apart, and, together with restriction digest patterns recorded for the same BAC clones, they provide immediate access to contigs of several hundred kilobases surrounding any gene of interest. The STCs survey >5% of the genome and provide the estimate that this genome contains approximately 27,350 protein-coding genes. The frequency distribution and canonical sequences of all middle and highly repetitive sequence families in the genome were obtained from the STCs as well. The 500-kb Hox gene complex of this species is being sequenced in its entirety. In addition, arrayed cDNA libraries of >10(5) clones each were constructed from every major stage of embryogenesis, several individual cell types, and adult tissues and are available to the community. The accumulated STC data and an expanding expressed sequence tag database (at present including >12, 000 sequences) have been reported to GenBank and are accessible on public web sites.

Aging↗

The evolution of embryonic patterning mechanisms in animals.

Animals exhibit an enormous diversity of life cycles and larval morphologies. The developmental basis for this diversity is not well understood. It is clear, however, that mechanisms of pattern formation in early embryos differ significantly among and within groups of animals. These differences show surprisingly little correlation with phylogenetic relationships; instead, many are correlated with ecological factors, such as changes in life histories.

Animals↗

Developmental regulatory genes and echinoderm evolution.

Modified interactions among developmental regulatory genes and changes in their expression domains are likely to be an important part of the developmental basis for evolutionary changes in morphology. Although developmental regulatory genes are now being studied in an increasing number of taxa, there has been little attempt to analyze the resulting data within an explicit phylogenetic context. Here we present comparative analyses of expression data from regulatory genes in the phylum Echinodermata, considering the implications for understanding both echinoderm evolution as well as the evolution of regulatory genes in general. Reconstructing the independent evolutionary histories of regulatory genes, their expression domains, their developmental roles, and the structures in which they are expressed reveals a number of distinct evolutionary patterns. A few of these patterns correspond to interpretations common in the literature, whereas others have received little prior mention. Together, the analyses indicate that the evolution of echinoderms involved: (1) the appearance of many apomorphic developmental roles and expression domains, some of which have plesiomorphic bilateral symmetry and others of which have apomorphic radial symmetry or left-right asymmetry; (2) the loss of some developmental roles and expression domains thought to be plesiomorphic for Bilateria; and (3) the retention of some developmental roles thought to be plesiomorphic for Bilateria, although with modification in expression domains. Some of the modifications within the Echinodermata concern adult structures; others, transient larval structures. Some changes apparently appeared early in echinoderm evolution (> 450 Ma), whereas others probably happened more recently (< 50 Ma). Cases of likely convergence in expression domains suggest caution when using developmental regulatory genes to make inferences about homology among morphological structures of distantly related taxa.

Animals↗

Evolutionary dissociations between homologous genes and homologous structures.

Phenotype is encoded in the genome in an indirect manner: each morphological structure is the product of many interacting genes, and most regulatory genes have several distinct developmental roles and phenotypic consequences. The lack of a simple and consistent relationship between homologous genes and structures has important implications for understanding correlations between evolutionary changes at different levels of biological organization. Data from a variety of organisms are beginning to provide intriguing glimpses of the complex evolutionary relationship between genotype and phenotype. Much attention has been devoted to remarkably conserved relationships between homologous genes and structures. However, there is increasing evidence that several kinds of evolutionary dissociations can evolve between genotype and phenotype, some of which are quite unexpected. The existence of these dissocations limits the degree to which it is possible make inferences about the homology of structures based solely on the expression of homologous genes.

Anatomy, Comparative↗

Promoter logic.

Explore the source record for details and available documents.

Animals↗

Cloning of zebrafish vsx1: expression of a paired-like homeobox gene during CNS development.

vsx1 is a homeobox gene encoding a paired-type homeodomain and a CVC domain that was originally cloned from an adult goldfish retinal library. We previously reported the spatiotemporal expression pattern of vsx1 in the adult and developing retina of zebrafish and goldfish, and we suggested that vsx1 plays a role in determining the cell fate and maintenance of retinal interneurons. Other related genes encoding a CVC domain, such as vsx2 (alx) and chx10, are expressed both within and outside the retina during development. In this study, we report the cloning of zebrafish vsx1 and its developmental expression in both retinal and nonretinal regions of the CNS in zebrafish embryos. vsx1 expression was detected in a subset of hindbrain and spinal cord neurons before it was expressed in the retina. At about the same time that retinal expression began, the level of vsx1 was decreased in the spinal cord. The expression of vsx1 was progressively restricted, and eventually it was detected only in the inner nuclear layer (INL) of the developing retina. The combined expression patterns of teleost vsx1 and vsx2 (alx) during early zebrafish development encompasses the expression pattern observed for murine Chx10, and indicates a partitioning of function for CVC genes in lower vertebrates.

Amino Acid Sequence↗

When is homology not homology?

Although genes have specific phenotypic consequences in a given species, this functional relationship can clearly change during the course of evolution. Many cases of evolutionary dissociations between homologous genes and homologous morphological features are now known. These dissociations have interesting and important implications for understanding the genetic basis for evolutionary change in morphology.

Animals↗

Radical alterations in the roles of homeobox genes during echinoderm evolution.

Echinoderms possess one of the most highly derived body architectures of all metazoan phyla, with radial symmetry, a calcitic endoskeleton, and a water vascular system. How these dramatic morphological changes evolved has been the subject of extensive speculation and debate, but remains unresolved. Because echinoderms are closely related to chordates and postdate the protostome/deuterostome divergence, they must have evolved from bilaterally symmetrical ancestors. Here we report the expression domains in echinoderms of three important developmental regulatory genes (distal-less, engrailed and orthodenticle), all of which encode transcription factors that contain a homeodomain. Our findings show that the reorganization of body architecture involved extensive changes in the deployment and roles of homeobox genes. These changes include modifications in the symmetry of expression domains and the evolution of several new developmental roles, as well as the loss of roles conserved between arthropods and chordates. Some of these modifications seem to have evolved very early in the history of echinoderms, whereas others probably evolved during the subsequent diversification of adult and larval morphology. These results demonstrate the evolutionary lability of regulatory genes that are widely viewed as conservative.

Animals↗

The origin and evolution of animal appendages.

Animals have evolved diverse appendages adapted for locomotion, feeding and other functions. The genetics underlying appendage formation are best understood in insects and vertebrates. The expression of the Distal-less (Dll) homeoprotein during arthropod limb outgrowth and of Dll orthologs (Dlx) in fish fin and tetrapod limb buds led us to examine whether expression of this regulatory gene may be a general feature of appendage formation in protostomes and deuterostomes. We find that Dll is expressed along the proximodistal axis of developing polychaete annelid parapodia, onychophoran lobopodia, ascidian ampullae, and even echinoderm tube feet. Dll/Dlx expression in such diverse appendages in these six coelomate phyla could be convergent, but this would have required the independent co-option of Dll/Dlx several times in evolution. It appears more likely that ectodermal Dll/Dlx expression along proximodistal axes originated once in a common ancestor and has been used subsequently to pattern body wall outgrowths in a variety of organisms. We suggest that this pre-Cambrian ancestor of most protostomes and the deuterostomes possessed elements of the genetic machinery for and may have even borne appendages.

Amino Acid Sequence↗

The evolution of echinoderm development is driven by several distinct factors.

We analyzed a comparative data base of gene expression, cell fate specification, and morphogenetic movements from several echinoderms to determine why developmental processes do and do not evolve. Mapping this comparative data onto explicit phylogenetic frameworks revealed three distinct evolutionary patterns. First, some evolutionary differences in development correlate well with larval ecology but not with adult morphology. These associations are probably not coincidental because similar developmental changes accompany similar ecological transformations on separate occasions. This suggests that larval ecology has been a potent influence on the evolution of early development in echinoderms. Second, a few changes in early development correlate with transformations in adult morphology. Because most such changes have occurred only once, however, it is difficult to distinguish chance associations from causal relationships. And third, some changes in development have no apparent phenotypic consequences and do not correlate with obvious features of either life history or morphology. This suggests that some evolutionary changes in development may evolve in a neutral or nearly neutral mode. Importantly, these hypotheses make specific predictions that can be tested with further comparative data and by experimental manipulations. Together, our phylogenetic analyses of comparative data suggest that at least three distinct evolutionary mechanisms have shaped early development in echinoderms.

Animals↗

Novel origins of lineage founder cells in the direct-developing sea urchin Heliocidaris erythrogramma.

The lineage and fate of each blastomere in the 32-cell embryo of the direct-developing sea urchin Heliocidaris erythrogramma have been traced by microinjection of tetramethylrhodamine-dextran. The results reveal substantive evolutionary modifications of the ancestral cell lineage pattern of indirect sea urchin development. Significant among these modifications are changes in the time and order of cell lineage segregation: vegetal ectodermal founder cells consistently arise earlier than during indirect development, while internal founder cells generally segregate later and in a different sequence. Modifications have also arisen in proportions of the embryo fated to become various cell types and larval structures. Ectodermal fates, particularly vestibular ectoderm, comprise a greater proportion of the total cellular volume in H. erythrogramma. Among internal cell types, coelom consumes more and endoderm less of the remaining cellular volume than during indirect sea urchin development. Evolutionary modifications are also apparent in the positional origin of larval cell types and structures in H. erythrogramma. These include an apparent tilt in the axis of prospective cell fate relative to the animal-vegetal axis as defined by cleavage planes. Together these evolutionary changes in the cell lineage of H. erythrogramma produce an accelerated loss of dorsoventral symmetry in cell fate relative to indirect development. The extent and diversity of rearrangements in its cell lineage indicate that the non-feeding larva of H. erythrogramma is a highly modified, novel form rather than a degenerate pluteus larva. These same modifications underscore the evolutionarily flexible relationship between cell lineage, gene expression, and larval morphology in sea urchin development.

Animals↗

The "lecithotrophic" sea urchin Heliocidaris erythrogramma lacks typical yolk platelets and yolk glycoproteins.

The sea urchin Heliocidaris tuberculata undergoes typical development, forming an echinoid pluteus larva, whereas H. erythrogramma undergoes direct development via a highly modified, nonfeeding larva. Using a polyclonal antibody prepared against yolk glycoproteins from the typical developer Stronglyocentrotus purpuratus, we found that H. tuberculata contains cross-reactive proteins in abundance, but H. erythrogramma does not. In addition, we used immunoelectron microscopy to demonstrate that unfertilized eggs of H. tuberculata contain yolk platelets, but those of H. erythrogramma do not.

Animals↗